Dysautonomia and dysosmia associated with anti-Hu antibodies induced by immune checkpoint inhibitors: a case report

Our plain-English summary of Dysautonomia and dysosmia associated with anti-Hu antibodies induced by immune checkpoint inhibitors: a case report, by M. Fujimoto, K. Igari, M. Fujimaki, et al (BMC Neurology, 2026).

The study

• Authors: M. Fujimoto, K. Igari, M. Fujimaki, S. Saiki
• Journal: BMC Neurology
• Published: 2026;26(1)
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

BACKGROUND: The use of immune checkpoint inhibitors may cause neurological immune-related adverse events in patients. Here, we report a case of autonomic nervous system involvement in nivolumab-induced autoimmune encephalitis with dysautonomia. CASE PRESENTATION: A 78-year-old man presented with a 4-month history of orthostatic hypotension, dysgeusia, and dysosmia following a 2-month course of nivolumab prescribed for malignant mesothelioma. Serum was positive for anti-neuronal nuclear antibody type 1. Diagnostic work-up, including imaging, neurological, and biochemical tests, suggested the diagnosis of nivolumab-induced autoimmune encephalitis with pronounced autonomic nervous system involvement. On day 10 of hospitalization, the patient received high-dose intravenous methylprednisolone followed by oral prednisone. The patient was discharged on day 29 with continued administration of corticosteroids and midodrine. At the 1-month outpatient follow-up, the patient remained stable and reported independent ambulation without marked orthostatic symptoms. CONCLUSIONS: We discuss a possible mechanism of dysautonomia in this case and draw attention to newly emerging autonomic symptoms and olfactory impairments during therapy with immune checkpoint inhibitors.

In plain English

This case report described one 78-year-old man who had earlier been treated for a malignant mesothelioma of the left scrotum and later received the immune checkpoint inhibitor nivolumab (240 mg every 2 weeks). After 2 months of nivolumab he developed low blood pressure on standing, a disturbed sense of taste and a reduced sense of smell. These had lasted 4 months when he presented. On standing, his blood pressure fell from 100/60 to 68/45 mmHg. Taste and smell testing showed severe loss. His blood tested positive for anti-Hu antibodies. Brain MRI showed a lesion in the right frontal region and, 2 weeks later, a new lesion in the left frontal lobe. The authors diagnosed nivolumab-induced autoimmune encephalitis with prominent autonomic involvement. He was treated with high-dose steroids and midodrine and discharged on day 29. One month later his blood pressure changed only slightly on standing, but his loss of smell persisted. The authors concluded that clinicians should watch for new autonomic symptoms and smell problems during this therapy. They noted that the exact site of nerve damage could not be identified. The article does not discuss asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (single patient)
• Who was studied: One 78-year-old man with a 4-month history of orthostatic hypotension, dysgeusia and dysosmia. Six years earlier he had had a malignant mesothelioma of the left scrotum resected. The authors are at the University of Tsukuba, Japan. No dates of care are given.
• Exposure: Nivolumab, an immune checkpoint inhibitor, 240 mg every 2 weeks for 2 months before neurological symptoms began. It was stopped 1 month after onset. He had earlier received cisplatin and pemetrexed, and later cisplatin-based chemotherapy, for the mesothelioma. No asbestos or fiber exposure is described.
• Main results:
  • Schellong test before treatment: blood pressure fell from 100/60 mmHg lying down to 68/45 mmHg on standing. Heart rate rose slightly, from 86 to 93 bpm.
  • Plasma norepinephrine rose from 241 pg/mL lying down to 530 pg/mL on standing. Arginine vasopressin rose from 1.3 to 3.5 pg/mL. The authors interpreted this as suggesting preganglionic autonomic dysfunction.
  • 123I-MIBG myocardial scintigraphy gave heart-to-mediastinum ratios of 2.02 (early phase) and 1.80 (late phase), against a normal value above 2.2. The authors took this to suggest impaired postganglionic sympathetic innervation.
  • Taste testing (electrogustometry) showed severe bilateral loss, with thresholds above 34 dB in the chorda tympani, glossopharynx and greater petrosal nerves.
  • Smell testing showed an elevated recognition threshold of 5.8, which the authors described as severe hyposmia.
  • Serum was positive for anti-Hu antibodies by immunoblot. Tissue-based immunofluorescence was reactive at a titer of 1:61440. Antibodies against the ganglionic acetylcholine receptor were negative.
  • Cognitive testing gave a Mini-Mental State Examination score of 23 of 30 and a Frontal Assessment Battery score of 13 of 18.
  • Brain MRI showed a hyperintense lesion in the right frontal cortex and white matter. A scan 2 weeks later showed a new white matter lesion in the left frontal lobe.
  • The patient scored 7 points on paraneoplastic neurological syndrome criteria, meeting the 'probable' level. Given the timing of nivolumab and no signs of infection or other malignancy, the authors diagnosed nivolumab-induced autoimmune encephalitis with prominent dysautonomia.
  • Treatment began on day 10 of hospitalization with intravenous methylprednisolone 1 g/day for 3 days, followed by oral prednisone 25 mg/day. A second course started on day 18, and oral midodrine 7.5 mg/day was added. He was discharged on day 29.
  • At 1-month follow-up, blood pressure went from 113/67 mmHg lying down to 102/73 mmHg on standing, and he walked independently.
  • At follow-up, the loss of smell persisted, with thresholds similar to the first test.
• The authors' conclusion: The authors concluded that autonomic dysfunction and loss of smell may be manifestations of neurological immune-related adverse events associated with anti-Hu antibodies. They said clinicians should watch for newly emerging autonomic symptoms and smell problems during immune checkpoint inhibitor therapy.
• Limitations the authors state:
  • The precise site of the autonomic lesion could not be identified.
  • Other autonomic function tests (sweating, gastrointestinal motility, bladder function) were not performed.
  • Antibody testing for autoimmune encephalitis was not done on the cerebrospinal fluid.
  • The best drug for treating this kind of low blood pressure remains uncertain.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Immune-Related Adverse Events, Nivolumab (Opdivo), Mesothelioma.

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